We are what we eat. In the modern world, there is much pressure to eat well and keep fit. The simple task of eating and surviving is made so much harder with the shifting of social norms to be thinner, while we find new ways to pack more calories in processed foods to satisfy our hunger and taste buds. When our eating becomes dysregulated, we can develop poor eating habits that make us dangerously underweight or morbidly obese.
The most prevalent eating disorders include anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Eating disorders disproportionately affect more females than males, and there is a rising epidemic in younger generations. These disorders are often not taken seriously and underreported,[36, 65] despite having a significant socio-economic impact,[23, 74] and can be lethal in many cases.[17, 23]
As mentioned, there is a worrying emerging trend of more young people, especially girls, being diagnosed with eating disorders.[36, 73] This is particularly concerning given it is a crucial time for physical development and eating disorders impose severe long-term consequences beyond body weight. Social pressures on body image contribute significantly to the development of eating disorders, exemplified by the high incidence of eating disorders in competitive sports/professional athletes, where the pressure to keep physically fit pushes individuals to adopt exercise and diet regimes leading to eating disorders.
Like all psychiatric conditions, biological bases for eating disorders are poorly understood and likely to be multifactorial. The lack of biological insight into these disorders renders them difficult to treat, thus placing a large burden on the affected, their careers, and the health system. Preclinical research allows stringent controls to test specific hypotheses, hence relevant animal models for eating disorders are essential to elucidate the causal biology to address the root of the issue and not just treating symptoms.
People suffering from AN have the belief that they are overweight when they are not, resulting in the persistent engagement of weight-loss behaviours such as starving themselves, excessive exercising, using substances to control appetite, and/or purge food out of the fear of gaining weight.[1, 4] Some also do not see being underweight, sometimes dangerously so, as a serious problem. AN has a prevalence of 1.9-2.6%, with females more likely to be affected than males. Unfortunately, AN has the highest mortality rate in all psychiatric disorders.[2, 17, 55]
For people who do not have AN, continued starvation tends to result in fatigue and slowness in action and thought. In contrast, starvation in AN does not appear to have a negative effect on general cognition and the patients continue to engage in high levels of physical activity for weight loss.[13, 58]
Given the fear of weight gain and the obsession with weight loss, it is no surprise that people suffering from AN also experience anxiety (including obsessive-compulsive disorder) and depression,[4, 14, 46] but the relationship between AN and these other psychiatric disorders are reciprocal, as starvation in healthy individuals can also lead to anxiety and depression.
There are a host of neurochemical, neuropeptide, and hormonal changes in AN; however, it is not clear if they are the cause or the effect of AN. For example, it is known there is a reduction of serotonin and differential expression of serotonin receptor subtypes in AN patients, yet selective serotonin reuptake inhibitors are ineffective in treating AN.
Symptoms leading to the diagnosis of BN are similar to those in AN – excessive dieting and exercise in an attempt to control body weight. The defining feature of BN is binge eating, followed by purging (mostly through vomiting). All these weight-control behaviours do not necessarily lead to weight loss, hence generating a sense of loss of control and shame for BN sufferers.
BN has high comorbidity with affective disorders like anxiety (especially PTSD) and depression, as well as substance use disorders. Prevalence of BN is 0.5-1.5%, with females reported to be 3-10 times more likely to be diagnosed with BN at any time.[35, 37]
Binge Eating Disorder
Persistent binge eating is a relatively “new” disorder with the designation of BED made in the latest version of the DSM-V. This is somewhat surprising given BED has the highest prevalence (2-3.5%) compared to BN and AN. In the clinic, BED is diagnosed when one (feels) they have lost control by eating too much in a short time, ignoring hunger and/or satiety cues (i.e., eating when not hungry and not stopping when full).
In contrast to BN, although the affected may be ashamed and become depressed about their binge eating, no action is taken to counteract the excessive intake of food (e.g., vomiting). As with other eating disorders, the lifetime prevalence in females (2.3%) is almost three times as high as in males (0.8%).
There is no clear and direct genetic influence in BED, owing to its relatively recent separate designation from BN, and the associations are often confounded with obesity. Behavioural and physical development traits and other medical conditions such as type 1 diabetes[66, 82] appear to increase the risk of BED diagnosis later in life, indicating potential genetic contributions.
Animal Models of Eating Disorders
In essence, given the development of pathological eating habits is driven by psychosocial factors (e.g., self-image, perceptions on food, and body weight), animals do not suffer from AN NB or BED as they are defined in humans. Animals do binge eat, but these tend to be functional in the context of survival (e.g., hibernation).
Introduction of other animals in the same environment in the wild (e.g., new conspecifics in the social group) or in the domesticated (e.g., new pets in a family home with resident pets) context may drive animals to over-eat, but the behaviour and hypothesised causes are not consistent with human BED.
Therefore, animal models of eating disorders are just that – reproducing physiological and/or behavioural changes which recapitulate some aspects of human pathology, but do not necessarily reflect the causal biology of the disorders.
Regardless, as all animal models of human diseases, animal models of eating disorders provide a way to test emerging hypotheses and generate new research avenues towards a better understanding of the diseases and their treatments – an important quest given existing treatments are only marginally effective.[21, 28, 52, 67]
Animal Models for Anorexia Nervosa
In as much as eating disorders are particularly difficult to model, activity-based anorexia (ABA) is perhaps the most relevant.[12, 29] Capturing both increased physical activity and reduced food intake despite hunger, rodents are rendered ABA by limiting feeding to a short period (60 minutes) with access to a running wheel for the rest of the time.[42, 62]
Furthermore, ABA rodents will eventually die from continued weight loss and malnutrition, and female rats tend to run more than male rats – recapitulating two salient features of AN. ABA is arguably the best AN (or any eating disorder) model given the parallel induction of voluntary starvation and increased exercise.
However, there is evidence the behaviours can be explained by physiological changes such as decreased body temperature and increased water consumption, which are not believed to be the root causes of maladaptive behaviours in AN.
Stress and eating disorders are biologically and clinically intertwined. With high comorbidities with affective disorders, stress models used to induce PTSD/depression-like symptoms also result in hypophagia. However, stress models recreate decreased food intake in AN, but not other hallmark symptoms such as increased physical activity.
There are many stress protocols to induce decreased feeding and weight loss including immobilisation,[45, 69] cold exposure,[10, 63] social isolation, exposure to novel environments, and social defeat. Stress models appear to converge on their modification to the hypothalamus-pituitary-adrenal (HPA) axis to control food intake.[38, 43]
Dietary Restriction Models
Significant weight loss is a direct consequence of decreased food intake. By restricting the amount of food available to the animals, it is possible to mimic the physiological consequences of starvation; however, decreased food intake is not voluntary and there is no significant increase in physical activity, thus limiting their relevance to AN. Regardless, there are various protocols ranging from sustained under-feeding[11, 24, 48] to feeding on alternate days or feeding only for a specific time period.
Given that the prevalence of AN has remained stable and appears to have a stronger genetic component[81, 85] than BN and BED, it is no surprise that AN has the more relevant genetic models out of the eating disorders. The anx/anx mice are the most used in AN research. An autosomal recessive spontaneous mutation results in a persistent, voluntary decrease in food consumption and hyperactivity to the extent that the mice do not survive for more than 3-4 weeks after birth. Although this model recapitulates the decreased eating and increased activity seen in AN, anx/anx mice suffer from neuropathology not seen in those affected by AN.
Melatonin-concentrating hormone knock-out mice have also been used in the study of AN. In this model, animals decrease food intake, lose weight, and have an elevated total energy expenditure.[59, 68] However, many of these animals also die from acute (48 hours) fasting and appear to have the same level of physical activity as control littermates, which are features not seen in AN. Mice with muscarinic receptor subtype 3 (M3) also exhibit a voluntary decrease in food intake and lower body mass but no change in physical activity levels.
It is worthwhile mentioning the corticotropin-releasing hormone receptor 2 (Crhr2) and cannabinoid receptor 1 (CB1) knockout mice. While neither knockouts display feeding abnormalities initially, both will develop voluntary under-eating after a bout of food restriction.[7, 25] These models display global phenotypes not consistent with AN but could serve as useful models to examine the induction of voluntary food restriction behaviour initiated by transient deprivation that is prevalent in AN and BN.
An interesting model combining genetic disposition (BDNF-Val66Met variant), gender (female), age (adolescent), stress induction, and food restriction – all important factors in AN, was able to recapitulate voluntary decrease in food consumption, some to the point of death. However, no increase in physical activity is evident in this model, despite a strong demonstration of construct validity and correspondence to potential human genetic risk.
A substrain of the Wistar rats, Lou/C rats display many biochemical and physiological changes[51, 79, 80] as seen in AN from their voluntary reduced food intake, decreased weight[56, 79], and increased physical activity. However, this model is not usually used in eating disorder modelling despite being well-matched to the main symptoms of AN, albeit in a milder phenotype; instead, the Lou/C rats is a model for “healthy aging”.
Bulimia Nervosa and Binge Eating Disorders
As rodents can’t vomit or do not naturally ingest laxatives in response to overfeeding, animal models of BN and BED are essentially models of binge eating.
Dietary Restriction Models
When food is restricted for a short time, rodents will overeat when food becomes available again, even if they are full and do not require to eat more to maintain their body weight. Although the model mimics the cycling between not eating and binge eating, the restriction of food intake is not voluntary as it is in BN. As for the “binge” eating, it is not manifested in the same way as in BN and BED, where binge eating is not driven by hunger but more by the rewarding aspects of eating.
Stress has been discussed above to induce decreased feeding in rodents. However, if food restriction is coupled with acute stress (like a footshock), animals will drastically increase palatable food intake. The implementation of the model is very specific – neither food restriction nor shock alone will induce bing-like eating,[3, 16] and there need be at least three rounds of food restriction and refeeding before the footshock to induce binge eating-like behaviour.
Interestingly, instead of acute shock, maternal separation can also serve as the source of the stress. Three rounds of food restriction/refeeding during development in maternally separated animals will also develop binge eating-like behaviour, despite not displaying such behaviour prior to the restriction/feeding cycles.
As pointed out earlier, one poignant feature of BN is purging the food after eating, which cannot be modelled in rodents since they do not possess the physical ability to vomit. One way to model the physiological process has been the use of a gastric fistula to drain the stomach contents as they enter to prevent absorption in the intestines.
This manipulation encourages excessive feeding. Of course, suffering from the same issues as other models of eating disorders, the purging of food is artificial and not voluntary, thus only suitable to study the physiological changes related to binge eating-like behaviour and not the causal or psychiatric aspects of BN and BED.
While the incidence of AN has remained relatively stable, binge eating prevalence appears to be on the rise since the 1950s. The assumption that a correlated increase in the variety and availability of more palatable, high-calorie foods playing a major role in the increase of BED and BN has translated well into animal models.[53, 60, 78] A particularly useful model for BED and BN imposes limited access to high-energy food in the absence of food restriction.[19, 26] In this setting, the access to high-fat food is restricted to two hours only, three times a week, and can be established in four weeks.
This model is highly relevant to BED and BN, as there is usually no change in body weight, animals voluntarily decrease the consumption of normal food (a way to control body weight without the option of purging; similar to the non-purging subtype of BN) and the binging/overeating behaviour is persistent. Although this model, like others, does not directly address the underlying causes of binge eating, it does provide an excellent platform for dissecting brain circuits related to binge eating with a bottom-up approach.
Other Eating Disorders
Avoidant/Restrictive Food Intake Disorder is a “new” eating disorder introduced in DSM-V with no current animal models. Pica is one of the more common eating disorders which is hard to model in rodents/animals in general, since chewing and ingesting things that are not food is functional and natural in animals.
Implementation of Animal Models
As discussed earlier, animal models of eating disorders mostly aim to artificially reproduce the physiological sequelae of their human disorder counterparts. While this “bottom-up” approach has yielded an improved understanding of motivation, appetite, and various homeostatic mechanisms in caloric intake and regulation of body weight, none address the “top-down” components (i.e., body image, shame, loss of control) which drive the maladaptive behaviours in eating disorders.
Being models of eating disorders, the primary physiological/behavioural measure is food intake. There are various ways this can be achieved:
1) number of responses to an operandum through conditioning/training the animals;
2) food delivery “eatometers” which counts the number of pellets delivered;
3) continuous monitoring of food hoppers with electronic scales;
4) detecting the presence of the animal in a designated feeding area;
5) contact-eatometers which detect access to food.
For AN, a parallel increase in physical activity is usually quantified by the number of revolutions made on a running wheel in the animal’s home cage. Several studies discussed here also used infrared beam-breaks to examine general changes in basal activity. Home cages with built-in activity sensors with capabilities to sample food consumption and other biometrics would be invaluable to control factors such as stress from handling.
Automated video behavioural analysis can be used to supplement activity/feeding measurements, as well as providing fine-grain behavioural analyses (e.g. abnormalities in grooming) for model characterisation. Various open fields can also be used to probe changes in the amount of locomotion, as well as anxiety for investigating comorbidities or as validation for stress induction models.
Stress can be induced in many ways, and different combinations of factors can yield AN or binge eating phenotypes. Foot shocks like those used in fear conditioning usually present a more PTSD-like phenotype and over-eating of more palatable food, while chronic unpredictable mild stress and social defeat protocols lead to a decrease in food intake.
Since in some of these models resilient animals do not display depression/PTSD-like behaviours (including anhedonia and reduced eating), validation experiments like sucrose preference test, social interaction tests, and other tests for anxiety may be needed to ensure homogeneity of the stressed group. All these tests are also useful in examining the high comorbidities eating disorders have with affective disorders.
As reiterated in this article, most of the eating disorder animal models only reproduce a very limited subset of symptoms in human disorders. The way symptoms are reproduced/modelled has very little resemblance to human behaviour apart from the changes in measured outcome (i.e., body weight and amount of food consumed).
Most of the time, only the physiological consequences can be studied adequately but not the psychological ones which hold the key to improved understanding of the diseases leading to efficacious treatment. There are other forms of eating disorders not discussed here, such as pica (eating things that are not food), avoidant/restrictive food intake disorder (pathological picky eating), and night eating syndrome – all of which are either in rodents’ normal behavioural repertoire or completely absent.
Eating disorders share high comorbidity with affective and substance abuse disorders, as well as conditions such as diabetes and obesity. The rising prevalence of these disorders warrants the exploration of more meaningful multi-factorial models which include genetic risk, stress induction, and recapitulation of main features of the human disease, instead of models which manipulate appetite to drive changes in food intake and body weight.
- American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013, Washington, DC.
- Arcelus, J, Mitchell, AJ, Wales, J, & Nielsen, S, Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies. Arch Gen Psychiatry, 2011. 68: 724-31.
- Artiga, AI, Viana, JB, Maldonado, CR, Chandler-Laney, PC, Oswald, KD, & Boggiano, MM, Body composition and endocrine status of long-term stress-induced binge-eating rats. Physiol Behav, 2007. 91: 424-31.
- Attia, E, Anorexia nervosa: current status and future directions. Annu Rev Med, 2010. 61: 425-35.
- Attia, E & Schroeder, L, Pharmacologic treatment of anorexia nervosa: where do we go from here? Int J Eat Disord, 2005. 37 Suppl: S60-3; discussion S87-9.
- Bailer, UF, Frank, GK, Henry, SE, Price, JC, Meltzer, CC, Mathis, CA, Wagner, A, Thornton, L, Hoge, J, Ziolko, SK, Becker, CR, McConaha, CW, & Kaye, WH, Exaggerated 5-HT1A but Normal 5-HT2A Receptor Activity in Individuals Ill with Anorexia Nervosa. Biological Psychiatry, 2007. 61: 1090-9.
- Bale, TL, Contarino, A, Smith, GW, Chan, R, Gold, LH, Sawchenko, PE, Koob, GF, Vale, WW, & Lee, KF, Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet, 2000. 24: 410-4.
- Boakes, RA & Juraskova, I, The role of drinking in the suppression of food intake by recent activity. Behav Neurosci, 2001. 115: 718-30.
- Brewerton, TD, Lydiard, RB, Herzog, DB, Brotman, AW, O’Neil, PM, & Ballenger, JC, Comorbidity of axis I psychiatric disorders in bulimia nervosa. J Clin Psychiatry, 1995. 56: 77-80.
- Brito, NA, Brito, MN, & Bartness, TJ, Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation. Am J Physiol Regul Integr Comp Physiol, 2008. 294: R1445-52.
- Bruss, MD, Khambatta, CF, Ruby, MA, Aggarwal, I, & Hellerstein, MK, Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates. Am J Physiol Endocrinol Metab, 2010. 298: E108-16.
- Carrera, O, Fraga, Á, Pellón, R, & Gutiérrez, E, Rodent model of activity-based anorexia. Curr Protoc Neurosci, 2014. 67: 9.47.1-11.
- Casper, RC, Behavioral activation and lack of concern, core symptoms of anorexia nervosa? International Journal of Eating Disorders, 1998. 24: 381-93.
- Casper, RC & Davis, JM, On the course of anorexia nervosa. The American Journal of Psychiatry, 1977. 134: 974-8.
- Cerrato, M, Carrera, O, Vazquez, R, Echevarría, E, & Gutierrez, E, Heat makes a difference in activity-based anorexia: a translational approach to treatment development in anorexia nervosa. Int J Eat Disord, 2012. 45: 26-35.
- Chandler-Laney, PC, Castañeda, E, Viana, JB, Oswald, KD, Maldonado, CR, & Boggiano, MM, A history of human-like dieting alters serotonergic control of feeding and neurochemical balance in a rat model of binge-eating. Int J Eat Disord, 2007. 40: 136-42.
- Chesney, E, Goodwin, GM, & Fazel, S, Risks of all-cause and suicide mortality in mental disorders: a meta-review. World Psychiatry, 2014. 13: 153-60.
- Cooper, Z & Fairburn, CG, Refining the definition of binge eating disorder and nonpurging bulimia nervosa. Int J Eat Disord, 2003. 34 Suppl: S89-95.
- Corwin, RL, Wojnicki, FHE, Fisher, JO, Dimitriou, SG, Rice, HB, & Young, MA, Limited Access to a Dietary Fat Option Affects Ingestive Behavior But Not Body Composition in Male Rats. Physiology & Behavior, 1998. 65: 545-53.
- Culbert, KM, Racine, SE, & Klump, KL, Research Review: What we have learned about the causes of eating disorders – a synthesis of sociocultural, psychological, and biological research. J Child Psychol Psychiatry, 2015. 56: 1141-64.
- Davis, H & Attia, E, Pharmacotherapy of eating disorders. Current Opinion in Psychiatry, 2017. 30.
- Davis, JD & Campbell, CS, Peripheral control of meal size in the rat. Effect of sham feeding on meal size and drinking rate. J Comp Physiol Psychol, 1973. 83: 379-87.
- Deloitte Access Economics, The Social and Economic Cost of Eating Disorders in the United States of America: A Report for the Strategic Training Initiative for the Prevention of Eating Disorders and the Academy for Eating Disorders. 2020. p. https://www.hsph.harvard.edu/striped/report-economic-costs-of-eating-disorders/.
- Devlin, MJ, Cloutier, AM, Thomas, NA, Panus, DA, Lotinun, S, Pinz, I, Baron, R, Rosen, CJ, & Bouxsein, ML, Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res, 2010. 25: 2078-88.
- Di Marzo, V, Goparaju, SK, Wang, L, Liu, J, Bátkai, S, Járai, Z, Fezza, F, Miura, GI, Palmiter, RD, Sugiura, T, & Kunos, G, Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature, 2001. 410: 822-5.
- Dimitriou, SG, Rice, HB, & Corwin, RL, Effects of limited access to a fat option on food intake and body composition in female rats. International Journal of Eating Disorders, 2000. 28: 436-45.
- Eddy, KT, Dorer, DJ, Franko, DL, Tahilani, K, Thompson-Brenner, H, & Herzog, DB, Diagnostic crossover in anorexia nervosa and bulimia nervosa: implications for DSM-V. Am J Psychiatry, 2008. 165: 245-50.
- Eddy, KT, Tabri, N, Thomas, JJ, Murray, HB, Keshaviah, A, Hastings, E, Edkins, K, Krishna, M, Herzog, DB, Keel, PK, & Franko, DL, Recovery From Anorexia Nervosa and Bulimia Nervosa at 22-Year Follow-Up. J Clin Psychiatry, 2017. 78: 184-9.
- Gutierrez, E, A rat in the labyrinth of anorexia nervosa: contributions of the activity-based anorexia rodent model to the understanding of anorexia nervosa. Int J Eat Disord, 2013. 46: 289-301.
- Hagan, MM, Chandler, PC, Wauford, PK, Rybak, RJ, & Oswald, KD, The role of palatable food and hunger as trigger factors in an animal model of stress induced binge eating. International Journal of Eating Disorders, 2003. 34: 183-97.
- Hagan, MM, Wauford, PK, Chandler, PC, Jarrett, LA, Rybak, RJ, & Blackburn, K, A new animal model of binge eating: key synergistic role of past caloric restriction and stress. Physiol Behav, 2002. 77: 45-54.
- Hao, S, Avraham, Y, Bonne, O, & Berry, EM, Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine. Pharmacol Biochem Behav, 2001. 68: 273-81.
- Hatsukami, D, Eckert, E, Mitchell, JE, & Pyle, R, Affective disorder and substance abuse in women with bulimia. Psychol Med, 1984. 14: 701-4.
- Hebebrand, J, Casper, R, Treasure, J, & Schweiger, U, The need to revise the diagnostic criteria for anorexia nervosa. J Neural Transm (Vienna), 2004. 111: 827-40.
- Hoek, HW & van Hoeken, D, Review of the prevalence and incidence of eating disorders. Int J Eat Disord, 2003. 34: 383-96.
- Hornberger, LL & Lane, MA, Identification and Management of Eating Disorders in Children and Adolescents. Pediatrics, 2021. 147: e2020040279.
- Hudson, JI, Hiripi, E, Pope, HG, Jr., & Kessler, RC, The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry, 2007. 61: 348-58.
- Jahng, JW, An animal model of eating disorders associated with stressful experience in early life. Horm Behav, 2011. 59: 213-20.
- Johansen, JE, Fetissov, S, Fischer, H, Arvidsson, S, Hökfelt, T, & Schalling, M, Approaches to anorexia in rodents: focus on the anx/anx mouse. Eur J Pharmacol, 2003. 480: 171-6.
- Kaye, WH, Frank, GK, Bailer, UF, & Henry, SE, Neurobiology of anorexia nervosa: Clinical implications of alterations of the function of serotonin and other neuronal systems. International Journal of Eating Disorders, 2005. 37: S15-S9.
- Keys, A, BroŽEk, J, Henschel, A, Mickelsen, O, Taylor, HL, Simonson, E, Skinner, AS, Wells, SM, Drummond, JC, Wilder, RM, King, CG, & Williams, RR, The Biology of Human Starvation Volume I. 1950: University of Minnesota Press.
- Klenotich, SJ & Dulawa, SC, The activity-based anorexia mouse model. Methods Mol Biol, 2012. 829: 377-93.
- Lo Sauro, C, Ravaldi, C, Cabras, PL, Faravelli, C, & Ricca, V, Stress, hypothalamic-pituitary-adrenal axis and eating disorders. Neuropsychobiology, 2008. 57: 95-115.
- Madra, M & Zeltser, LM, BDNF-Val66Met variant and adolescent stress interact to promote susceptibility to anorexic behavior in mice. Translational psychiatry, 2016. 6: e776-e.
- Martí, O, Martí, J, & Armario, A, Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure. Physiol Behav, 1994. 55: 747-53.
- Mattar, L, Huas, C, Duclos, J, Apfel, A, & Godart, N, Relationship between malnutrition and depression or anxiety in Anorexia Nervosa: A critical review of the literature. Journal of Affective Disorders, 2011. 132: 311-8.
- Meerlo, P, Overkamp, GJ, Daan, S, Van Den Hoofdakker, RH, & Koolhaas, JM, Changes in Behaviour and Body Weight Following a Single or Double Social Defeat in Rats. Stress, 1996. 1: 21-32.
- Méquinion, M, Caron, E, Zgheib, S, Stievenard, A, Zizzari, P, Tolle, V, Cortet, B, Lucas, S, Prévot, V, Chauveau, C, & Viltart, O, Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction? Am J Physiol Endocrinol Metab, 2015. 308: E241-55.
- Micali, N, Field, AE, Treasure, JL, & Evans, DM, Are obesity risk genes associated with binge eating in adolescence? Obesity (Silver Spring), 2015. 23: 1729-36.
- Micali, N, Hagberg, KW, Petersen, I, & Treasure, JL, The incidence of eating disorders in the UK in 2000-2009: findings from the General Practice Research Database. BMJ Open, 2013. 3.
- Mitchell, SE, Nogueiras, R, Rance, K, Rayner, DV, Wood, S, Dieguez, C, & Williams, LM, Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats. J Endocrinol, 2006. 190: 571-9.
- Murray, SB, Quintana, DS, Loeb, KL, Griffiths, S, & Le Grange, D, Treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of randomized controlled trials. Psychol Med, 2019. 49: 535-44.
- Murray, SM, Tulloch, AJ, Chen, EY, & Avena, NM, Insights revealed by rodent models of sugar binge eating. CNS Spectr, 2015. 20: 530-6.
- Nilsson, IA, Thams, S, Lindfors, C, Bergstrand, A, Cullheim, S, Hökfelt, T, & Johansen, JE, Evidence of hypothalamic degeneration in the anorectic anx/anx mouse. Glia, 2011. 59: 45-57.
- Papadopoulos, FC, Ekbom, A, Brandt, L, & Ekselius, L, Excess mortality, causes of death and prognostic factors in anorexia nervosa. Br J Psychiatry, 2009. 194: 10-7.
- Perrin, D, Soulage, C, Pequignot, JM, & Géloën, A, Resistance to obesity in Lou/C rats prevents ageing-associated metabolic alterations. Diabetologia, 2003. 46: 1489-96.
- Pirke, KM, Broocks, A, Wilckens, T, Marquard, R, & Schweiger, U, Starvation-induced hyperactivity in the rat: The role of endocrine and neurotransmitter changes. Neuroscience & Biobehavioral Reviews, 1993. 17: 287-94.
- Pirke, KM, Trimborn, P, Platte, P, & Fichter, M, Average total energy expenditure in anorexia nervosa, bulimia nervosa, and healthy young women. Biol Psychiatry, 1991. 30: 711-8.
- Qu, D, Ludwig, DS, Gammeltoft, S, Piper, M, Pelleymounter, MA, Cullen, MJ, Mathes, WF, Przypek, R, Kanarek, R, & Maratos-Flier, E, A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature, 1996. 380: 243-7.
- Razzoli, M, Pearson, C, Crow, S, & Bartolomucci, A, Stress, overeating, and obesity: Insights from human studies and preclinical models. Neurosci Biobehav Rev, 2017. 76: 154-62.
- Ribasés, M, Gratacòs, M, Fernández-Aranda, F, Bellodi, L, Boni, C, Anderluh, M, Cristina Cavallini, M, Cellini, E, Di Bella, D, Erzegovesi, S, Foulon, C, Gabrovsek, M, Gorwood, P, Hebebrand, J, Hinney, A, Holliday, J, Hu, X, Karwautz, A, Kipman, A, Komel, R, Nacmias, B, Remschmidt, H, Ricca, V, Sorbi, S, Tomori, M, Wagner, G, Treasure, J, Collier, DA, & Estivill, X, Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations. Eur J Hum Genet, 2005. 13: 428-34.
- Routtenberg, A & Kuznesof, AW, Self-starvation of rats living in activity wheels on a restricted feeding schedule. Journal of Comparative and Physiological Psychology, 1967. 64: 414-21.
- Rowland, N, Effects of chronic cold exposure on wheel running, food intake and fatty acid synthesis in Syrian hamsters. Physiol Behav, 1984. 33: 253-6.
- Saegusa, Y, Takeda, H, Muto, S, Nakagawa, K, Ohnishi, S, Sadakane, C, Nahata, M, Hattori, T, & Asaka, M, Decreased plasma ghrelin contributes to anorexia following novelty stress. Am J Physiol Endocrinol Metab, 2011. 301: E685-96.
- Santomauro, DF, Melen, S, Mitchison, D, Vos, T, Whiteford, H, & Ferrari, AJ, The hidden burden of eating disorders: an extension of estimates from the Global Burden of Disease Study 2019. The Lancet Psychiatry, 2021. 8: 320-8.
- Scheuing, N, Bartus, B, Berger, G, Haberland, H, Icks, A, Knauth, B, Nellen-Hellmuth, N, Rosenbauer, J, Teufel, M, & Holl, RW, Clinical characteristics and outcome of 467 patients with a clinically recognized eating disorder identified among 52,215 patients with type 1 diabetes: a multicenter german/austrian study. Diabetes Care, 2014. 37: 1581-9.
- Shapiro, JR, Berkman, ND, Brownley, KA, Sedway, JA, Lohr, KN, & Bulik, CM, Bulimia nervosa treatment: a systematic review of randomized controlled trials. Int J Eat Disord, 2007. 40: 321-36.
- Shimada, M, Tritos, NA, Lowell, BB, Flier, JS, & Maratos-Flier, E, Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature, 1998. 396: 670-4.
- Shimizu, N, Oomura, Y, & Kai, Y, Stress-induced anorexia in rats mediated by serotonergic mechanisms in the hypothalamus. Physiol Behav, 1989. 46: 835-41.
- Smith, GP, Animal models of human eating disorders. Ann N Y Acad Sci, 1989. 575: 63-72; discussion -4.
- Sonneville, KR, Calzo, JP, Horton, NJ, Field, AE, Crosby, RD, Solmi, F, & Micali, N, Childhood hyperactivity/inattention and eating disturbances predict binge eating in adolescence. Psychol Med, 2015. 45: 2511-20.
- Soulage, C, Zarrouki, B, Soares, AF, Lagarde, M, & Geloen, A, Lou/C Obesity-resistant Rat Exhibits Hyperactivity, Hypermetabolism, Alterations in White Adipose Tissue Cellularity, and Lipid Tissue Profiles. Endocrinology, 2008. 149: 615-25.
- Stice, E, Marti, CN, & Rohde, P, Prevalence, incidence, impairment, and course of the proposed DSM-5 eating disorder diagnoses in an 8-year prospective community study of young women. Journal of Abnormal Psychology, 2013. 122: 445-57.
- Streatfeild, J, Hickson, J, Austin, SB, Hutcheson, R, Kandel, JS, Lampert, JG, Myers, EM, Richmond, TK, Samnaliev, M, Velasquez, K, Weissman, RS, & Pezzullo, L, Social and economic cost of eating disorders in the United States: Evidence to inform policy action. International Journal of Eating Disorders, 2021. n/a.
- Sundgot-Borgen, J & Torstveit, MK, Prevalence of Eating Disorders in Elite Athletes Is Higher Than in the General Population. Clinical Journal of Sport Medicine, 2004. 14.
- Swanson, SA, Crow, SJ, Le Grange, D, Swendsen, J, & Merikangas, KR, Prevalence and correlates of eating disorders in adolescents. Results from the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry, 2011. 68: 714-23.
- Tagay, S, Schlottbohm, E, Reyes-Rodriguez, ML, Repic, N, & Senf, W, Eating disorders, trauma, PTSD, and psychosocial resources. Eat Disord, 2014. 22: 33-49.
- Treasure, J, Leslie, M, Chami, R, & Fernández-Aranda, F, Are trans diagnostic models of eating disorders fit for purpose? A consideration of the evidence for food addiction. European Eating Disorders Review, 2018. 26: 83-91.
- Veyrat-Durebex, C, Montet, X, Vinciguerra, M, Gjinovci, A, Meda, P, Foti, M, & Rohner-Jeanrenaud, F, The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue. Am J Physiol Endocrinol Metab, 2009. 296: E1120-32.
- Veyrat-Durebex, C, Poher, AL, Caillon, A, Somm, E, Vallet, P, Charnay, Y, & Rohner-Jeanrenaud, F, Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the Lou/C rat. PLoS One, 2013. 8: e73452.
- Watson, HJ, Yilmaz, Z, Thornton, LM, Hübel, C, Coleman, JRI, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Medland, SE, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Purves, KL, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Baker, JH, Berrettini, WH, Boehm, I, Boni, C, Perica, VB, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OSP, de Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, Gallinger, S, Giegling, I, Giuranna, J, Gonidakis, F, Gorwood, P, Mayora, MG, Guillaume, S, Guo, Y, Hakonarson, H, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Kaprio, J, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, Y-R, Klareskog, L, Klump, KL, Knudsen, GPS, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, Mattingsdal, M, McDevitt, S, McGuffin, P, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, K, Monteleone, AM, Monteleone, P, Munn-Chernoff, MA, Nacmias, B, Navratilova, M, Ntalla, I, O’Toole, JK, Ophoff, RA, Padyukov, L, Palotie, A, Pantel, J, Papezova, H, Pinto, D, Rabionet, R, Raevuori, A, Ramoz, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op ‘t Landt, MCT, Slopien, A, Sorbi, S, Świątkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, JE, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Stuber, GD, Gordon, S, Grove, J, Henders, AK, Juréus, A, Kirk, KM, Larsen, JT, Parker, R, Petersen, L, Jordan, J, Kennedy, M, Montgomery, GW, Wade, TD, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Martin, NG, Mortensen, PB, Sullivan, PF, Breen, G, Bulik, CM, Anorexia Nervosa Genetics, I & Eating Disorders Working Group of the Psychiatric Genomics, C, Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics, 2019. 51: 1207-14.
- Wisting, L, Frøisland, DH, Skrivarhaug, T, Dahl-Jørgensen, K, & Rø, O, Disturbed eating behavior and omission of insulin in adolescents receiving intensified insulin treatment: a nationwide population-based study. Diabetes Care, 2013. 36: 3382-7.
- Yamada, M, Miyakawa, T, Duttaroy, A, Yamanaka, A, Moriguchi, T, Makita, R, Ogawa, M, Chou, CJ, Xia, B, Crawley, JN, Felder, CC, Deng, CX, & Wess, J, Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature, 2001. 410: 207-12.
- Yilmaz, Z, Gottfredson, NC, Zerwas, SC, Bulik, CM, & Micali, N, Developmental Premorbid Body Mass Index Trajectories of Adolescents With Eating Disorders in a Longitudinal Population Cohort. J Am Acad Child Adolesc Psychiatry, 2019. 58: 191-9.
- Yilmaz, Z, Hardaway, JA, & Bulik, CM, Genetics and Epigenetics of Eating Disorders. Adv Genomics Genet, 2015. 5: 131-50.
- Zgheib, S, Méquinion, M, Lucas, S, Leterme, D, Ghali, O, Tolle, V, Zizzari, P, Bellefontaine, N, Legroux-Gérot, I, Hardouin, P, Broux, O, Viltart, O, & Chauveau, C, Long-term physiological alterations and recovery in a mouse model of separation associated with time-restricted feeding: a tool to study anorexia nervosa related consequences. PLoS One, 2014. 9: e103775.